Apparatus for Trans-Cerebral Electrophoresis and Methods of Use Thereof

Abstract

The present invention provides apparatus and methods for the delivery of therapeutic agents to target tissues by electromigration. The utilization of electric fields according to the methods of the invention aids in the distribution and targeting of therapeutic agents, in particular, where standard means of agent application in the target tissue is insufficient to achieve prophylactic or therapeutic results. In particular embodiments, the present invention utilizes a convective force in combination with the developed electric fields to further increase the flux of the therapeutic agent or to further improve distribution of the therapeutic agent within the target tissues.

Description

1. INTRODUCTIONThe present invention provides apparatus and methods for the delivery of therapeutic agents to target tissues through the use of electric fields. The utilization of electric fields according to the methods of the invention aids in the distribution and targeting of therapeutic agents, in particular, where standard means of agent application is insufficient or impractical to reach target tissues. In particular embodiments, the present invention utilizes a convective force in combination with the developed electric fields to further increase the flux or distribution of the therapeutic agent within the target tissues.2. BACKGROUND OF THE INVENTIONThe ability to treat neurological and mental disorders is limited, in part, by the ability to deliver therapeutic compounds efficiently to the brain parenchyma. Pharmaceuticals are delivered to the majority of bodily tissues via the oral (PO), intramuscular (IM) or intravenous (IV) routes. When these mechanisms prove insufficient...

AI Technical Summary

Benefits of technology

In certain embodiments, the integrated TCE cannulas of the invention are suitable for agent administration in accordance with the methods of CEDD as known in the art. The integrated TCE cannula of the invention combines the function of an infusion catheter for CEDD and one or more electrophoretic electrodes. Having at least one of the polarizable electrodes of the electrode array at the site of agent administration allows the developed electric field to be modulated to better focus, direct and / or regulate agent dispersal to or within the target site. As described herein, in addition to the integrated TCE cannula, the invention comprises one or more monopolar electrodes separate from that of the implantable, integrated TCE cannula having a connector for connecting to a power source. When the array of electrodes is connected to the power source and separately polarized, the electric field is generated by the array. The invention also encompasses methods of use of the apparatus described herein for delivery of an agent to a target tissue within the CNS of a subject, e.g., for the treatment, prevention or amelioration of one or more symptoms of a CNS disease or disorder.

Problems solved by technology

The ability to treat neurological and mental disorders is limited, in part, by the ability to deliver therapeutic compounds efficiently to the brain parenchyma.

These delivery routes are relatively ineffective for disorders of the central nervous system (CNS) because of the blood-brain barrier (BBB).

Unfortunately, the BBB also impedes the delivery of therapeutic agents via the blood, creating unique difficulties for treating most neurological disorders.

Although numerous strategies have been devised to disrupt or bypass the BBB, the lack of clinically relevant methods indicates that improved methods are necessary.

However, even if CEDD proves effective in delivering therapeutic agents to small tissue volumes, the technique may not be scalable, leaving numerous brain disorders that may require treatment of much greater tissue volumes unaffected.

For example, reported failures of CEDD infusions of glial derived neurotropic factor (GDNF) for the treatment of Parkinson's disease may have been caused by inadequate distribution of the GDNF infusate within the putamen rather than a failure of the GDNF to generate the desired biological effect.

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